Genetic studies of insulin-dependent diabetes mellitus: segregation and linkage analyses

Tissue Antigens
A GreenM Hauge

Abstract

The inclusion of HLA data in genetic studies of insulin-dependent diabetes mellitus (IDDM) has not led to conclusive segregation models for IDDM so far. As a new approach, we first applied complex segregation analysis, independently of HLA data, to two combined Danish family materials. Then the best fitting segregation model was entered into linkage analysis of a third material, including family as well as HLA data. The best solution obtained in the segregation analysis was a mixed model, including an intermediate gene, which on the penetrance scale acts as a recessive, together with a polygenic component. The linkage analysis showed an overall recombination fraction of 0.0417 with high coupling frequencies for the HLA-DR3 and HLA-DR4 alleles and the putative disease susceptibility gene. However, when the pedigrees were divided according to whether or not the proband had the heterozygous HLA-phenotype DR3/DR4, a maximum likelihood ratio test for heterogeneity was significant, with estimated recombination fractions of 0.0 and 0.0963 in HLA-DR3/DR4 pedigrees and the remaining pedigrees, respectively. In total, we found convincing evidence that two familial factors contribute to IDDM: a locus within HLA, which very well may be DR;...Continue Reading

References

Jan 1, 1979·Human Heredity·C ZavalaR Lisker
Jul 1, 1978·Annals of Human Genetics·B Degnbol, A Green
Oct 1, 1980·Annals of Human Genetics·R S SpielmanC M Zmijewski
Dec 1, 1980·Journal of Epidemiology and Community Health·D C PoskanzerM S Park
Dec 1, 1980·Journal of Epidemiology and Community Health·D C PoskanzerM S Park
Jan 1, 1981·Human Heredity·N E Morton, J M Lalouel
Jan 1, 1981·Human Heredity·J M Lalouel, N E Morton
Nov 1, 1979·Tissue Antigens·J BarbosaL Greenberg

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Citations

Jan 1, 1983·Molecular Aspects of Medicine·N R FaridJ C Bear
Jul 19, 1984·The New England Journal of Medicine·J H WarramC R Kahn
May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·P Liò, N E Morton
Jul 31, 2008·American Journal of Medical Genetics. Part a·Gene S Fisch
Jan 1, 1983·Immunological Reviews·S W Serjeantson
Jan 1, 1983·Immunological Reviews·A SvejgaardL P Ryder
Jul 1, 1987·Diabetes/metabolism Reviews·M L Hoover, J D Capra
Dec 1, 1995·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·I KockumA Lernmark

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